In the field of blood transfusion, blood component transfusion comprising separating a blood component necessary for a recipient from a whole blood product and transfusing the blood component into the recipient has been commonly practiced in addition to whole blood transfusion comprising transfusing a whole blood product, obtained by adding an anticoagulant to blood collected from a donor, into a recipient The blood component transfusion is classified into red cell transfusion, platelet transfusion, plasma transfusion, and the like depending on the type of the blood component necessary for a recipient. The blood product used for the blood component transfusion includes a red cell product, platelet product, plasma product, and the like.
In recent years, leukocyte-free blood transfusion in which a blood product is transfused after removing leukocytes contained in the blood product has been widely used. This is because it was found that relatively slight side effects accompanying blood transfusion, such as headache, nausea, chill, or febrile nonhemolytic reaction, or serious side effects which seriously affect a recipient, such as alloantigen sensitization, viral infection, or posttransfusion graft versus host disease (GVHD), are mainly caused by leukocytes contained in the blood product used for blood transfusion.
It is considered that relatively slight side effects such as headache, nausea, chill, or fever can be prevented by removing leukocytes in the blood product until the leukocyte residual rate becomes 10-1 to 10-2 or less. It is considered that leukocytes must be removed until the residual rate becomes 10-4 to 10-6 or less in order to prevent serious side effects such as alloantigen sensitization or viral infection.
In recent years, leukocyte removal therapy using extracorporeal blood circulation has been conducted for treating diseases such as rheumatism or ulcerative colitis, and has achieved excellent clinical effects.
Methods of removing leukocytes from the blood product are roughly classified into two kinds of methods of a centrifugation method in which leukocytes are separated and removed using a centrifuge by utilizing the difference in specific gravity among blood components, and a filter method in which leukocytes are removed by using a filter material comprising fiber mass such as nonwoven fabric, a porous structure having continuous pores or the like. The filter method which removes leukocytes by means of adhesion or adsorption is most widely used at present because this method has advantages such as simplified operation and low cost.
In the leukocyte removal mechanism using the filter material such as fiber mass such as nonwoven fabric or a porous structure having continuous pores, it is considered that leukocytes coming into contact with the surface of the filter material adhere to or are adsorbed on the surface of the filter material. Therefore, as means for improving the leukocyte removal performance of the conventional filter material, a method of increasing the contact frequency between the filter material and leukocytes, specifically, studies of reducing the fiber diameter or the pore size of the nonwoven fabric or increasing the bulk density have been proceeded (Japanese Patent No. 1723513 (JP-1723513)). However, since the pressure drop is increased when causing the blood product to pass through the filter material accompanying improvement of the leukocyte removal performance, there has been a problem that the filtration speed is significantly decreased before completing the filtration of a desired amount of blood.
On the other hand, as to the porous structure having continuous pores, a porous product having a bubble point of 0.08 to 0.3 kg/cm2 is disclosed as a leukocyte separation material free from clogging with leukocytes (Japanese Patent Application Laid-Open No. 01-224324 (JP-A-01-224324)). However, the inventors of the present invention examined and found that this leukocyte separation material is suitable for reducing leukocytes contained in the blood product to 10−2 to 10−3, but poses the following problem when using a porous product having a relatively small average pore size necessary for achieving a leukocyte residual rate of 10−4 which is the target value of the present invention. Specifically, a porous product with an optimal pore size exhibits a leukocyte removal performance equal to that of nonwoven fabric at a thickness several times smaller than that of the nonwoven fabric, and may provide promising means in achieving a reduction in size. However, a porous product exhibiting such a high leukocyte removal performance shows a large degree of pressure drop due to clogging with leukocytes, whereby the blood filtration speed is significantly decreased in the same manner as in the case of using nonwoven fabric having a small fiber diameter.
In recent years, the medical treatment field has posed additional demands for the leukocyte removal filter. One of the demands is improvement of the recovery rate of useful components in addition to improvement of the leukocyte removal performance. At present, useful components remaining in the filter and the circuit are collected by using a physiological saline solution or air in order to increase the recovery rate of useful components. However, it is important to save labor by making such an operation unnecessary. Blood as the raw material for the blood product is mainly valuable blood provided by a goodwill blood donation. However, uncollectible blood remaining in the leukocyte removal filter is disposed of together with the filter and frittered away. Therefore, it is extremely meaningful to improve the recovery rate of useful components in comparison with the existing leukocyte removal filter.
Therefore, in order to satisfy the above-described demand in the medical treatment field, a leukocyte removal filter device using a leukocyte removal filter material having a high leukocyte removal performance per unit volume and packed with a smaller amount of filter material than ever before has been demanded. Use of such a device reduces the amount of blood remaining in the filter due to a reduction in the amount of filter material packed and makes it unnecessary to perform the operation of collecting useful components remaining in the filter, whereby the recovery rate of useful components is expected to be increased in comparison with a conventional filter device.
As another demand for the leukocyte removal filter in the market, there is a demand for treating a desired amount of blood in a short period of time. In order to satisfy such a demand, the leukocyte removal filter device is considered to have such a shape that the cross-sectional area of the device is equal to or greater than that of a conventional device and the thickness of the filter material is reduced. However, it is necessary to increase the leukocyte removal performance per unit volume in order to reduce the thickness of the filter material while maintaining the leukocyte removal performance.
In order to satisfy such demands, attempts to improve the leukocyte removal performance per unit volume have been made by improving uniformity of the property elements of the filter material. As a general filter material in which the property elements are made uniform, a nonwoven fabric filter material in which the pore size of the nonwoven fabric used as the filter material is made uniform and the pore size distribution in which fibers having different thicknesses exist is made narrow, nonwoven fabric of which the fiber diameter is uniform, which does not include overlapping fibers, and of which weight per square meter (metsuke) is made uniform, and the like can be given (JP-A-63-175156, JP-A-09-155127, and WO 96/03194).
In the technical field aiming at removing leukocytes, as a material in which the property elements of the filter material are made uniform, a leukocyte trapping material in which the volume of the pore section useful for leukocyte removal is increased by narrowing the pore size distribution, and a three-dimensional mesh-like continuous porous product having a uniform pore size in which the ratio of the volume average pore size to the number average pore size is 1.5 to 2.5 have been proposed. As nonwoven fabric as the filter material, nonwoven fabric in which uniformity of the fiber diameter is improved by narrowing the fiber diameter distribution has been proposed (WO 93/03740, JP-A-07-124255, JP-A-63-175157, and JP-2811707).
As described above, attempts to increase the leukocyte removal performance per unit volume have been proceeded by making the pore size or the fiber diameter of the filter material uniform. However, the leukocyte removal performance of the leukocyte removal filter or flowability during filtration is not necessarily improved by making the pore size or the fiber diameter of the filter material uniform. Specifically, since blood flows through the filter material in the thickness direction, if the property elements of the filter material in the thickness direction are nonuniform in the filtration surface direction, blood tends to flow through the portion of the filter material in which the liquid-flow resistance is low, even if the pore size or the fiber diameter is uniform. As a result, since filtration is completed without the entire filter material being uniformly utilized, a sufficient leukocyte removal performance cannot be obtained. Moreover, since clogging tends to occur in the portion in which a large amount of blood flows due to a decrease in the substantial liquid-flow area, the filtration time is increased. Therefore, the leukocyte removal performance per unit volume is improved in a microscopic sense by making the pore size or the fiber diameter uniform. However, in a macroscopic sense, if the pores in the nonwoven fabric as the filter material are not uniformly arranged, or the fiber is unevenly distributed, or the weight per square meter of the filter material is nonuniform, since blood tends to flow through the portion having a low liquid-flow resistance, a sufficient filter performance cannot be achieved. As described above, the conventional technologies merely intend to make a single property element represented by the fiber diameter and the average pore size uniform, but do not recognize the importance of uniformity over the entire filter material.